DESCRIPTION: "Molecular container compounds," the carcerands and hemicarcerands, are molecules created and synthesized primarily by Donald J. Cram and his research group. The principal investigator notes that the goals of this research are (1) to understand the novel phenomena which have been discovered for these molecules, (2) to better understand analogous biological processes and to develop computational methods for their study, and (3) to design new molecular containers for potential biomedical applications. Dr. Houk indicates that using modern computational and simulation techniques, he will study the binding of neutral guest molecules in carcerand hosts. Force-field, molecular dynamics, and free-energy perturbation methods are to be used to calculate geometries, energy barriers for conformational and complexation processes, and equilibrium constants for complexation. It is noted that the processes by which molecules pass into and out of the cavities of hemicarcerands are simple analogs to important biological processes, such as the passage of substrates and products in and out of enzymes and that the understanding of these processes, and the computational methods developed for their study will be used to design new molecular containers for potential biomedical applications. The principal investigator indicates that he will design carcerands and hemicarcerands as possible drug delivery vehicles, as molecular sensing devices for biological and environmental applications, and as artificial receptors for the selective binding of small neutral molecules. It is stated that this research will lead to (1) the development and parameterization of methods to understand and design molecular recognition involving neutral molecules, (2) the understanding of the stabilities and dynamic processes of hemicarceplexes and carceplexes, (3) the calibration of methods for the investigation of interactions of substrates and inhibitors with biological macromolecules (4) the design of hemicarceplexes to act as devices for biomedical applications, and (5) the experimental testing of the most promising of these designs.